Accuracy of Biomarker Testing for Neuropathologically Defined Alzheimer Disease in Older Adults With Dementia.

BACKGROUND: Biomarker accuracy for Alzheimer disease (AD) is uncertain. PURPOSE: To summarize evidence on biomarker accuracy for classifying AD in older adults with dementia. DATA SOURCES: Electronic bibliographic databases (searched from January 2012 to November 2019 for brain imaging and cerebrospinal fluid [CSF] tests and from inception to November 2019 for blood tests), ClinicalTrials.gov (to November 2019), and systematic review bibliographies. STUDY SELECTION: English-language studies evaluating the accuracy of brain imaging, CSF testing, or blood tests for distinguishing neuropathologically defined AD from non-AD among older adults with dementia. Studies with low or medium risk of bias were analyzed. DATA EXTRACTION: Two reviewers rated risk of bias. One extracted data; the other verified accuracy. DATA SYNTHESIS: Fifteen brain imaging studies and 9 CSF studies met analysis criteria. Median sensitivity and specificity, respectively, were 0.91 and 0.92 for amyloid positron emission tomography (PET), 0.89 and 0.74 for 18F-labeled fluorodeoxyglucose (18F-FDG) PET, 0.64 and 0.83 for single-photon emission computed tomography, and 0.91 and 0.89 for medial temporal lobe atrophy on magnetic resonance imaging (MRI). Individual CSF biomarkers and ratios had moderate sensitivity (range, 0.62 to 0.83) and specificity (range, 0.53 to 0.69); in the few direct comparisons, ß-amyloid 42 (Aß42)/phosphorylated tau (p-tau) ratio, total tau (t-tau)/Aß42 ratio, and p-tau appeared more accurate than Aß42 and t-tau alone. Single studies suggested that amyloid PET, 18F-FDG PET, and CSF test combinations may add accuracy to clinical evaluation. LIMITATIONS: Studies were small, biomarker cut points and neuropathologic AD were inconsistently defined, and methods with uncertain applicability to typical clinical settings were used. Few studies directly compared biomarkers, assessed test combinations, evaluated whether biomarkers improved classification accuracy when added to clinical evaluation, or reported harms. CONCLUSION: In methodologically heterogeneous studies of uncertain applicability to typical clinical settings, amyloid PET, 18F-FDG PET, and MRI were highly sensitive for neuropathologic AD. Amyloid PET, 18F-FDG PET, and CSF test combinations may add accuracy to clinical evaluation. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018117897).

Efficacy and Safety of Testosterone Treatment in Men: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians.

Background: Testosterone treatment rates in adult men have increased in the United States over the past 2 decades. Purpose: To assess the benefits and harms of testosterone treatment for men without underlying organic causes of hypogonadism. Data Sources: English-language searches of multiple electronic databases (January 1980 to May 2019) and reference lists from systematic reviews. Study Selection: 38 randomized controlled trials (RCTs) of at least 6 months' duration that evaluated transdermal or intramuscular testosterone therapies versus placebo or no treatment and reported prespecified patient-centered outcomes, as well as 20 long-term observational studies, U.S. Food and Drug Administration review data, and product labels that reported harms information. Data Extraction: Data extraction by a single investigator was confirmed by a second, 2 investigators assessed risk of bias, and evidence certainty was determined by consensus. Data Synthesis: Studies enrolled mostly older men who varied in age, symptoms, and testosterone eligibility criteria. Testosterone therapy improved sexual functioning and quality of life in men with low testosterone levels, although effect sizes were small (low- to moderate-certainty evidence). Testosterone therapy had little to no effect on physical functioning, depressive symptoms, energy and vitality, or cognition. Harms evidence reported in trials was judged to be insufficient or of low certainty for most harm outcomes. No trials were powered to assess cardiovascular events or prostate cancer, and trials often excluded men at increased risk for these conditions. Observational studies were limited by confounding by indication and contraindication. Limitation: Few trials exceeded a 1-year duration, minimum important outcome differences were often not established or reported, RCTs were not powered to assess important harms, few data were available in men aged 18 to 50 years, definitions of low testosterone varied, and study entry criteria varied. Conclusion: In older men with low testosterone levels without well-established medical conditions known to cause hypogonadism, testosterone therapy may provide small improvements in sexual functioning and quality of life but little to no benefit for other common symptoms of aging. Long-term efficacy and safety are unknown. Primary Funding Source: American College of Physicians. (PROSPERO: CRD42018096585).

Brief Cognitive Tests for Distinguishing Clinical Alzheimer-Type Dementia From Mild Cognitive Impairment or Normal Cognition in Older Adults With Suspected Cognitive Impairment.

BACKGROUND: The accuracy and harms of brief cognitive tests for identifying clinical Alzheimer-type dementia (CATD) are uncertain. PURPOSE: To summarize evidence on accuracy and harms of brief cognitive tests for CATD in older adults with suspected cognitive impairment. DATA SOURCES: Electronic bibliographic databases (from inception to November 2019) and systematic review bibliographies. STUDY SELECTION: English-language, controlled observational studies in older adults that evaluated the accuracy of brief cognitive tests (standalone tests; memory, executive function, and language tests; and brief multidomain batteries) for distinguishing CATD from mild cognitive impairment (MCI) or normal cognition as defined by established diagnostic criteria. Studies with low or medium risk of bias (ROB) were analyzed. DATA EXTRACTION: Two reviewers rated ROB. One reviewer extracted data; the other verified extraction accuracy. DATA SYNTHESIS: Fifty-seven studies met analysis criteria. Many brief, single cognitive tests were highly sensitive and specific for distinguishing CATD from normal cognition. These included standalone tests (clock-drawing test, median sensitivity 0.79 and specificity 0.88 [8 studies]; Mini-Mental State Examination, 0.88 and 0.94 [7 studies]; Montreal Cognitive Assessment, 0.94 and 0.94 [2 studies]; and Brief Alzheimer Screen, 0.92 and 0.97 [1 study]), memory tests (list delayed recall, 0.89 and 0.94 [5 studies]), and language tests (category fluency, 0.92 and 0.89 [9 studies]). Accuracy was lower in distinguishing mild CATD from normal cognition and distinguishing CATD from MCI. No studies reported on testing harms. LIMITATIONS: Studies were small. Few test metrics were evaluated by multiple studies. Few studies directly compared different tests, scores, cut points, or test combinations. CONCLUSION: Many brief, single cognitive tests accurately distinguish CATD from normal cognition in older adults but are less accurate in distinguishing mild CATD from normal cognition or CATD from MCI. No studies reported on testing harms. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018117897).

Enhanced Recovery Protocols for Adults Undergoing Colorectal Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: Enhanced surgical recovery protocols are designed to reduce hospital length of stay and health care costs. OBJECTIVE: This study aims to systematically review and summarize evidence from randomized and controlled clinical trials comparing enhanced recovery protocols versus usual care in adults undergoing elective colorectal surgery with emphasis on recent trials, protocol components, and subgroups for surgical approach and colorectal condition. DATA SOURCES: MEDLINE from 2011 to July 2017; reference lists of existing systematic reviews and included studies were reviewed to identify all eligible trials published before 2011. STUDY SELECTION: English language trials comparing a protocol of preadmission, preoperative, intraoperative, and postoperative components with usual care in adults undergoing elective colorectal surgery were selected. INTERVENTION: The enhanced recovery protocol for colorectal surgery was investigated. MAIN OUTCOME MEASURES: Length of stay, perioperative morbidity, mortality, readmission within 30 days, and surgical site infection were the primary outcomes measured. RESULTS: Twenty-five trials of open or laparoscopic surgery for cancer or noncancer conditions were included. Enhanced recovery protocols consisted of 4 to 18 components. Few studies fully described the various components. Length of stay (mean reduction, 2.6 days; 95% CI, -3.2 to -2.0) and risk of overall perioperative morbidity (risk ratio, 0.66; 95% CI, 0.54-0.80) were lower in enhanced recovery protocol groups than in usual care groups (moderate-quality evidence). All-cause mortality (rare), readmissions, and surgical site infection rates were similar between protocol groups (low-quality evidence). In predefined subgroup analyses, findings did not vary by surgical approach (open vs laparoscopic) or colorectal condition. LIMITATIONS: Protocols varied across studies and little information was provided regarding compliance with, or implementation of, specific protocol components. CONCLUSIONS: Enhanced recovery protocols for adults undergoing colorectal surgery improve patient outcomes with no increase in adverse events. Evidence was insufficient regarding which components, or component combinations, are key to improving patient outcomes. PROSPERO registration number: CRD42017067991.

Screening for, monitoring, and treatment of chronic kidney disease stages 1 to 3: a systematic review for the U.S. Preventive Services Task Force and for an American College of Physicians Clinical Practice Guideline.

BACKGROUND: Screening and monitoring for chronic kidney disease (CKD) could lead to earlier interventions that improve clinical outcomes. PURPOSE: To summarize evidence about the benefits and harms of screening for and monitoring and treatment of CKD stages 1 to 3 in adults. DATA SOURCES: MEDLINE (1985 through November 2011), reference lists, and expert suggestions. STUDY SELECTION: English-language, randomized, controlled trials that evaluated screening for or monitoring or treatment of CKD and that reported clinical outcomes. DATA EXTRACTION: Two reviewers assessed study characteristics and rated quality and strength of evidence. DATA SYNTHESIS: No trials evaluated screening or monitoring, and 110 evaluated treatments. Angiotensin-converting enzyme inhibitors (relative risk, 0.65 [95% CI, 0.49 to 0.88]) and angiotensin II-receptor blockers (relative risk, 0.77 [CI, 0.66 to 0.90]) reduced end-stage renal disease versus placebo, primarily in patients with diabetes who have macroalbuminuria. Angiotensin-converting enzyme inhibitors reduced mortality versus placebo (relative risk, 0.79 [CI, 0.66 to 0.96]) in patients with microalbuminuria and cardiovascular disease or high-risk diabetes. Statins and ß-blockers reduced mortality and cardiovascular events versus placebo or control in patients with impaired estimated glomerular filtration rate and either hyperlipidemia or congestive heart failure, respectively. Risks for mortality, end-stage renal disease, or other clinical outcomes did not significantly differ between strict and usual blood pressure control. The strength of evidence was rated high for angiotensin II-receptor blockers and statins, moderate for angiotensin-converting enzyme inhibitors and ß-blockers, and low for strict blood pressure control. LIMITATIONS: Evidence about outcomes was sometimes scant and derived from post hoc analyses of subgroups of patients enrolled in trials. Few trials reported or systematically collected information about adverse events. Selective reporting and publication bias were possible. CONCLUSION: The role of CKD screening or monitoring in improving clinical outcomes is uncertain. Evidence for CKD treatment benefit is strongest for angiotensin-converting enzyme inhibitors and angiotensin II-receptor blockers, and in patients with albuminuria combined with diabetes or cardiovascular disease. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Teledermatology for diagnosis and management of skin conditions: a systematic review.

OBJECTIVE: We performed a systematic review of the literature addressing teledermatology: (1) diagnostic accuracy/concordance; (2) management accuracy/concordance; (3) clinical outcomes; and (4) costs. METHODS: Peer-reviewed controlled trials published in English between 1990 and 2009 were identified through MEDLINE and PubMed searches. RESULTS: Of 78 included studies, approximately two-thirds comparing teledermatology and clinic dermatology found better diagnostic accuracy with clinic dermatology. Diagnostic concordance of store and forward with clinic dermatology was good; concordance rates for live interactive and clinic dermatology were higher, but based on fewer patients. Overall rates of management accuracy were equivalent, but teledermatology and teledermatoscopy were inferior to clinic dermatology for malignant lesions. Management concordance was fair to excellent. There was insufficient evidence to evaluate clinical course outcomes. Patient satisfaction and preferences were comparable. Teledermatology reduced time to treatment and clinic visits and was cost-effective if certain assumptions were met. LIMITATIONS: Heterogeneity in studies (design, skin conditions, outcomes) limited the ability to pool data. CONCLUSION: The benefits of teledermatology need to be evaluated in the context of potential limitations.

Ground Reaction Forces in Children's Gait.

Ground reaction force patterns during walking were observed in 18 children 3 and 4 years of age. The children walked barefoot at a self-chosen walking pace. Selected variables representing the vertical, anteroposterior, and mediolateral force components were evaluated. The results indicated that children in this age range contact the ground with greater vertical force measures relative to body mass than do adults. In addition, the minimum vertical force was lower, the transition from braking to propulsion occurred earlier, and the mediolateral force excursions were higher than typically found in adults. When the children were divided into groups on the basis of sex, differences were observed between those groups. The boys exhibited a greater difference in the vertical peak forces, a lower minimum force, a greater braking force, and a higher mediolateral force excursion value. The results indicated that children display a different ground reaction force pattern than do adults and that differences between boys and girls may be observed as early as ages 3 and 4 years.